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Nutritional management of older adults with gastrointestinal cancers: An International Society of Geriatric Oncology (SIOG) review paper

Open AccessPublished:February 01, 2018DOI:https://doi.org/10.1016/j.jgo.2018.01.003

      Abstract

      Malnutrition is one of the most common physical manifestations of gastrointestinal (GI) cancers and is often under-diagnosed and under-treated. Like cancers, malnutrition occurs more commonly in older adults, with potential negative consequences to quality of life, functional status, tolerance to treatment, and prognosis. Nutritional assessment and management require a proactive and systematic, multi-disciplinary approach. Early assessment, detection, and prompt intervention of cancer–associated malnutrition and cachexia are equally essential to achieve better quality nutritional care for older oncology patients. This article aims to provide an overview of the evidence associated with poor nutrition and outcomes in older adults with GI cancers, and recommends a management approach from a geriatric oncologist's perspective.

      Keywords

      1. Overview of the Evidence Associated With Poor Nutrition and Outcomes in Older Patients With Gastrointestinal Cancers

      Almost 30% of cancer incidence and 32% of cancer deaths worldwide are due to gastrointestinal (GI) malignancies, [
      • Ferlay J.
      • Soerjomataram I.
      • Ervik M.
      • et al.
      GLOBOCAN 2012 v1.0, cancer incidence and mortality worldwide: IARC CancerBase no. 11 [Internet].
      ] and both incidence and mortality rise exponentially with age. The aging process is associated with sarcopenia, comorbidities with associated loss of functional reserve of multiple organ systems, and increased vulnerability to frailty [
      • Balducci L.
      • Colloca G.
      • Cesari M.
      • et al.
      Assessment and treatment of elderly patients with cancer.
      ]. Poor nutritional status is a known poor prognostic factor in patients with malignancies [
      • Arends J.
      • Baracos V.
      • Bertz H.
      • et al.
      ESPEN expert group recommendations for action against cancer-related malnutrition.
      ,
      • Pressoir M.
      • Desne S.
      • Berchery D.
      • et al.
      Prevalence, risk factors and clinical implications of malnutrition in French Comprehensive Cancer Centres.
      ], causing a significant concern as the risk of cancer and malnutrition are more common in an older population [
      • Lacau St Guily J.
      • Bouvard E.
      • Raynard B.
      • et al.
      NutriCancer: a French observational multicentre cross-sectional study of malnutrition in elderly patients with cancer.
      ]. In general, approximately 10–20% of cancer deaths can be attributed to malnutrition rather than the cancer itself [
      • Pressoir M.
      • Desne S.
      • Berchery D.
      • et al.
      Prevalence, risk factors and clinical implications of malnutrition in French Comprehensive Cancer Centres.
      ,
      • Ottery F.D.
      Cancer cachexia: prevention, early diagnosis, and management.
      ,
      • von Haehling S.
      • Anker S.D.
      Cachexia as a major underestimated and unmet medical need: facts and numbers.
      ]. The French National Authority for Health defined malnutrition in older adults as one or more of the following: ≥5% weight loss in 1 month or ≥10% in 6 months, and/or Mini-Nutritional Assessment (MNA) score of <17/30, and/or serum albumin <35 g/L, and/or body mass index (BMI) of <21 kg/m2 [
      • HAS
      Haute Autorité de Santé. Nutritional Support Strategy for Protein-Energy Malnutrition in the Elderly.
      ]. However, a BMI ≥21 does not exclude the diagnosis of malnutrition, such as in the case of sarcopenic obesity [
      • Batsis J.A.
      • Sahakyan K.R.
      • Rodriguez-Escudero J.P.
      • et al.
      Normal weight obesity and mortality in United States subjects >/=60 years of age (from the Third National Health and Nutrition Examination Survey).
      ]. Age >70 years and malnutrition increase the risk of death 2–2.5 times, respectively [
      • Pressoir M.
      • Desne S.
      • Berchery D.
      • et al.
      Prevalence, risk factors and clinical implications of malnutrition in French Comprehensive Cancer Centres.
      ]. However, in older patients, it is often more difficult to delineate age-related versus tumor–related effects on malnutrition. In addition to underrepresentation in clinical trials and lack of management consensus guidelines, very few oncologic papers distinguish young from older adults and the age cut-off values often vary, making their management rather challenging. This article reviews the current evidence supporting the negative impact of poor nutrition on the management outcomes of patients including older adults, with a specific focus on GI cancers. We systematically identified studies published in English over the last decade on the nutritional status of older adults with GI cancers through PubMed and MEDLINE databases, by combining search terms “malnutrition”, “sarcopenia”, “screening”, “GI cancer”, and “elderly”. Additional articles were identified from citations in the articles that were evaluated. As the terminology relating to malnutrition varies, specific terms and definitions used in this manuscript are defined in Table 1.
      Table 1Terminology.
      (Adapted from
      • Arends J.
      • Baracos V.
      • Bertz H.
      • et al.
      ESPEN expert group recommendations for action against cancer-related malnutrition.
      ,
      • Fearon K.
      • Strasser F.
      • Anker S.D.
      • et al.
      Definition and classification of cancer cachexia: an international consensus.
      .)
      EtiologyIntervention
      AnorexiaLimited food intake from altered CNS appetite signals related to disease or its treatment, or from structural or functional limitations to food intake (i.e. mucositis, obstruction, altered intestinal transit, etc.)Pharmacologic agents
      StarvationLoss of body fat & non-fat mass caused by poor protein-energy or nutrient intakeAdequate nutritional support
      SarcopeniaReduction or loss of skeletal muscle mass and strength with aging, which may lead to functional impairmentPhysical exercise

      High protein and energy diet
      Cancer cachexiaInvoluntary multifactorial wasting of protein or energy stores and skeletal muscle mass, with or without loss of fat mass.

      Release of pro-inflammatory cytokines results in significant weight loss, altered body composition, and decline in physical function
      Physical exercise

      High protein and energy diet

      Anti-inflammatory agents Anti-cancer treatment
      CNS = central nervous system.

      1.1 Sarcopenia

      The aging process is associated with sarcopenia, a gradual and progressive loss of skeletal muscle mass leading to reduced strength or physical performance [
      • Cruz-Jentoft A.J.
      • Baeyens J.P.
      • Bauer J.M.
      • et al.
      Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People.
      ] that is commonly seen in sedentary older adults. Sarcopenia has an estimated prevalence of 30% among adults >60 years [
      • Doherty T.J.
      Invited review: aging and sarcopenia.
      ] and a decline in muscle mass is expected at a rate of up to 15% per decade at ≥70 years of age [
      • Kim T.N.
      • Choi K.M.
      Sarcopenia: definition, epidemiology, and pathophysiology.
      ]. It accelerates the risk for developing adverse outcomes such as functional impairment and disability [
      • Delmonico M.J.
      • Harris T.B.
      • Lee J.-S.
      • et al.
      Alternative definitions of sarcopenia, lower extremity performance, and functional impairment with aging in older men and women.
      ,
      • Goodpaster B.H.
      • Park S.W.
      • Harris T.B.
      • et al.
      The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study.
      ], poor quality of life (QoL) and death [
      • Cruz-Jentoft A.J.
      • Baeyens J.P.
      • Bauer J.M.
      • et al.
      Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People.
      ], and its effect could be magnified in the presence of malignancy. Regular aerobic and resistance exercises, along with adequate protein and energy intake have been shown to help counteract the effects of age-related decline in muscle mass, strength, and function in healthy older adults [
      • Deutz N.E.
      • Bauer J.M.
      • Barazzoni R.
      • et al.
      Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group.
      ]. Specific to cancers, sarcopenia has often led to worse outcomes, including increased risk for developing 5-FU and capecitabine-related ≥ grade 2 toxicities [
      • Prado C.M.
      • Baracos V.E.
      • McCargar L.J.
      • et al.
      Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity.
      ,
      • Prado C.M.
      • Baracos V.E.
      • McCargar L.J.
      • et al.
      Sarcopenia as a determinant of chemotherapy toxicity and time to tumor progression in metastatic breast cancer patients receiving capecitabine treatment.
      ], the mainstay of treatment for most GI cancers, and a 2-fold increased mortality for patients with colorectal cancer (CRC) with >5% muscle loss post-chemotherapy [
      • Miyamoto Y.
      • Baba Y.
      • Sakamoto Y.
      • et al.
      Negative impact of skeletal muscle loss after systemic chemotherapy in patients with unresectable colorectal cancer.
      ]. Table 2 summarises the negative consequences of sarcopenia in GI cancers.
      Table 2Consequences of malnutrition in studies including older patients with GI cancers.
      Disease

      Author, year (reference)
      Study designPrimary endpointStudy population, n

      Age in years
      Treatment regimen givenResults
      Sarcopenic rateOutcome
      Esophageal or esophagogastric cancer
      Anadavadivelan et al., 2016
      • Anandavadivelan P.
      • Brismar T.B.
      • Nilsson M.
      • et al.
      Sarcopenic obesity: a probable risk factor for dose limiting toxicity during neo-adjuvant chemotherapy in oesophageal cancer patients.
      Retrospective dataset from a prospectively collected data

      Multicentre
      Association between sarcopenia and/or sarcopenic obesity and DLT after cycle 1 CTn = 72

      Age: 67 ± 7

      Resectable disease
      Neoadjuvant Cisplatin + 5-FU43%

      Sarcopenic obesity: 14%
      Increased DLT with sarcopenic obese (OR 5.54; p = 0.04)
      Tamandl et al., 2016
      • Tamandl D.
      • Paireder M.
      • Asari R.
      • et al.
      Markers of sarcopenia quantified by computed tomography predict adverse long-term outcome in patients with resected oesophageal or gastro-oesophageal junction cancer.
      Retrospective data from hospital information system

      Single centre
      Impact of sarcopenia on survival post-surgeryn = 200

      Median age: 63.9
      Surgery65%Worse OS
      • Sarcopenia: HR 1.87, p = 0.011
      • 40 HU muscle attenuation: HR 1.91, p = 0.019
      • FMi: HR 3.47, p = 0.016
      Tan et al., 2015
      • Tan B.H.
      • Brammer K.
      • Randhawa N.
      • et al.
      Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer.
      Retrospective data from MDT

      Single centre
      Predictors of DLTn = 89

      Age: 65.8 ± 8.1

      Potentially curative, locally advanced disease
      Neoadjuvant CT: ECX or CF49%Sarcopenia
      • more common in older patients (68.6 ± 7 years vs. 63.1 ± 8.3 years)
      • higher DLT (54.5% vs. 28.9%; p = 0.015)
      • lower median OS (569 vs. 1013 days); p = 0.04
      • no difference in OS in patients with DLT independent of sarcopenia
      Gastric cancer
      Aahlin et al., 2017
      • Aahlin E.
      • Irino T.
      • Johns N.
      • et al.
      Body composition indices and tissue loss in patients with resectable gastric adenocarcinoma.
      Retrospective analysis of patient files

      Two centres
      Skeletal muscle index and outcomesn = 137

      Median age: 70
      Periop CT (EOX or ECX regimen) + surgery45%Reduction in lean tissue mass during neoadjuvant CT (p = 0.001)

      Poor OS in patients with low preop skeletal muscle index (HR 1.91, p = 0.019)
      Palmela et al., 2017
      • Palmela C.
      • Velho S.
      • Agostinho L.
      • et al.
      Body composition as a prognostic factor of neoadjuvant chemotherapy toxicity and outcome in patients with locally advanced gastric cancer.
      Retrospective data from electronic records

      Single centre
      Prevalence of sarcopenia and association with CT toxicity and long-term outcomesn = 48

      Age: 68 ± 10
      Neoadjuvant CT23%

      Sarcopenic obesity: 10%
      Age > 65: lower muscle attenuation

      DLT: 46%

      Sarcopenia:
      • Increased CT termination (OR 4.23, p = 0.05)
      Sarcopenic obesity:
      • Lower OS (6 vs. 25 months, p = 0)
      Qiu et al., 2015
      • Qiu M.
      • Zhou Y.X.
      • Jin Y.
      • et al.
      Nutrition support can bring survival benefit to high nutrition risk gastric cancer patients who received chemotherapy.
      Prospective data from NRS

      Single centre
      Prevalence and prognostic value of nutrition risk (all stages) and nutritional support (stage IV only)n = 830

      70: 401 (48%)
      CT50.7 (NRS ≥3)
      • Longer median OS for NRS <3: 31.9 vs. 25.7 months, p < 0.001
      • NRS shift with nutritional support: 30.3%
      • Improved median survival with NRS shift: 14.3 vs. 9.6 months; p = 0.001
      Seo et al., 2016
      • Seo S.H.
      • Kim S.E.
      • Kang Y.K.
      • et al.
      Association of nutritional status-related indices and chemotherapy-induced adverse events in gastric cancer patients.
      Retrospective study of medical records

      Single centre
      Association of nutritional status indices with CT-induced adverse eventsn = 234

      >65: 38 (26%)
      Adjuvant CT59%
      • LBM and low albumin increased risk for grade 3 or 4 hematological toxicities
      • Age was an independent risk factor for grade 3 or 4 non-hematological toxicities
      Hepatocellular cancer
      Harimoto et al., 2016
      • Harimoto N.
      • Yoshizumi T.
      • Shimokawa M.
      • et al.
      Sarcopenia is a poor prognostic factor following hepatic resection in patients aged 70 years and older with hepatocellular carcinoma.
      Retrospective data from clinical records

      Single centre
      Outcomes of sarcopenia in ≥70 years post-hepatic resectionn = 296

      70: 139 (47%)
      Hepatectomy37.8%

      Age ≥ 70: 41%
      Significantly poorer OS in patients ≥70 with sarcopenia
      • sarcopenia
      • Child-Pugh B
      • Multiple tumors
      • Poor differentiation
      Significantly poorer DFS in patients ≥70 with sarcopenia
      • Sarcopenia
      • Stage III or IV
      Blood transfusion
      Voron et al., 2015
      • Voron T.
      • Tselikas L.
      • Pietrasz D.
      • et al.
      Sarcopenia impacts on short- and long-term results of hepatectomy for hepatocellular carcinoma.
      Retrospective analysis of prospectively maintained computer database

      Single centre
      Prognostic factors on liver surgeryn = 109

      Age: 61.6 ± 13.3

      60: 38 (64%)
      Liver surgery54%Sarcopenia:
      • more common in older patients (p = 0.013)
      • 71.2 vs. 40% disease recurrence (p = 0.002)
      • 34 vs. 14% deaths at 21.23 months median follow-up
      • shorter median PFS (10.1 vs. 34.23 months, p < 0.001)
      • shorter median OS (52.3 vs. 70.3 months, p = 0.015)
      • poorer OS (HR = 3.19, p = 0.013)
      Colorectal cancer
      Aaldriks et al., 2013
      • Aaldriks A.A.
      • van der Geest L.G.
      • Giltay E.J.
      • et al.
      Frailty and malnutrition predictive of mortality risk in older patients with advanced colorectal cancer receiving chemotherapy.
      Prospective analysis of patient records

      Multicentre
      GA to predict tolerance & feasibility of treatment with adjuvant or palliative CTn = 143

      Median age: 75 (70–92)

      70–79: 88%

      ≥80: 12%
      Adjuvant CT: 38%

      Palliative CT: 62%
      28%Toxicities: 78%

      MNA <23.5
      • Adjuvant CT: 20%
      • Palliative CT: 33%
      Mortality (15 months median follow-up) among patients receiving palliative CT
      • 2.76-fold risk in MNA <23.5 (p < 0.001)
      • 2.72-fold risk in GFI frail
      Ali et al., 2016
      • Ali R.
      • Baracos V.E.
      • Sawyer M.B.
      • et al.
      Lean body mass as an independent determinant of dose-limiting toxicity and neuropathy in patients with colon cancer treated with FOLFOX regimens.
      Prospective data from physician's notes

      Multicentre
      Toxicity associated with LBM during first 4 cycles

      DLT if ≥Gr 3 or ≥Gr 2 for neuropathy
      n = 138

      Age: 61.5 ± 10.3

      Stage IV
      FOLFOX or FOLFIRINOX ± cetuximab40%Dose ≥3.55 mg oxaliplatin/kg ↑ risk for DLT

      25% of DLT was due to neuropathy
      Barret et al., 2014
      • Barret M.
      • Antoun S.
      • Dalban C.
      • et al.
      Sarcopenia is linked to treatment toxicity in patients with metastatic colorectal cancer.
      Prospective, cross-sectional study based on patient records

      Multicentre
      Effect of sarcopenia on CT toxicityn = 51

      Age: 65 (22–84)

      Stage IV
      FP ± oxaliplatin or irinotecan or irinotecan alone71%Sarcopenia was significantly associated with grade 3 or 4 toxicities (OR 13.55; p = 0.043)
      Jung et al., 2015
      • Jung H.W.
      • Kim J.W.
      • Kim J.Y.
      • et al.
      Effect of muscle mass on toxicity and survival in patients with colon cancer undergoing adjuvant chemotherapy.
      Analysis of prospectively maintained cancer registry

      Single centre
      Effect of decreased muscle mass on toxicity & survivaln = 299

      60: 127 (55%)

      Stage III
      Adjuvant oxaliplatin, 5-FU, leucovorinObesity

      BMI ≥ 25: 19%
      1 SD decrement in PI was associated with increased in all grade 3–4 toxicities (OR 1.56) and overall mortality (OR 1.85)

      Higher mortality with:
      • age ≥60 (HR 2.94; p = 0.028)
      • BMI ≥25 (HR 4.35; p = 0.011)
      Miyamoto et al., 2015
      • Miyamoto Y.
      • Baba Y.
      • Sakamoto Y.
      • et al.
      Negative impact of skeletal muscle loss after systemic chemotherapy in patients with unresectable colorectal cancer.
      Retrospective data from patient records

      Single centre
      Prognostic value of skeletal muscle mass pre-CT and rate of skeletal muscle change in cross-sectional area post-CTn = 182

      70: 54 (30%)

      Unresectable disease
      1st line CT ± targeted therapy20%Median follow-up, months

      PFS: 8.1

      OS: 23.2

      Skeletal muscle loss >5% post-CT was significantly associated with poorer PFS and OS
      Prado et al., 2007
      • Prado C.M.
      • Baracos V.E.
      • McCargar L.J.
      • et al.
      Body composition as an independent determinant of 5-fluorouracil-based chemotherapy toxicity.
      Prospective data from patient records

      Single centre
      Predictor of toxicities after cycle 1n = 62

      Age: 60.3 ± 9.9

      High risk stage II or stage III
      Adjuvant 5-FU and leucovorin20 mg 5FU/kg LBM is a significant predictor of overall toxicity (OR 16.75; p = 0.013)
      Pancreatic cancer
      Wu et al., 2014
      • Wu W.
      • He J.
      • Cameron J.L.
      • et al.
      The impact of postoperative complications on the administration of adjuvant therapy following pancreaticoduodenectomy for adenocarcinoma.
      Retrospective chart review

      Single centre
      Impact of postoperative complications to TTA of adjuvant therapyn = 1144

      Median age: 68

      >68: 48.6%
      Adjuvant CTOverall complication rate: 49%
      • >68 years: 53%
      TTA: 60 days

      Overall adjuvant therapy rate: 54.2%
      • >68 years: 39.7%
      Median OS: 18.1 months
      • 68 vs. >68 years: 20 vs. 15 months (p < 0.001)

      1.2 Cachexia

      Cachexia is provisionally defined as ≥5% involuntary weight loss over 6 months; or BMI <20 and any degree of weight loss ≥ 2%; or sarcopenia and any degree of weight loss >2% [
      • Fearon K.
      • Strasser F.
      • Anker S.D.
      • et al.
      Definition and classification of cancer cachexia: an international consensus.
      ]. Although, such a definition has gained some popularity among clinicians, it does not account for the different BMI thresholds between younger and older adults [
      • Hebuterne X.
      • Bermon S.
      • Schneider S.M.
      Ageing and muscle: the effects of malnutrition, re-nutrition, and physical exercise.
      ,
      • Raynaud-Simon A.
      • Revel-Delhom C.
      • Hebuterne X.
      • et al.
      Clinical practice guidelines from the French Health High Authority: nutritional support strategy in protein-energy malnutrition in the elderly.
      ,
      • ANAES
      Clinical Practice Guidelines: diagnostic assessment of protein-energy malnutrition in hospitalized adults.
      ]. Moreover, refractory cachexia, a syndrome commonly defined as irreversible and unresponsive to nutritional interventions [
      • Arends J.
      • Baracos V.
      • Bertz H.
      • et al.
      ESPEN expert group recommendations for action against cancer-related malnutrition.
      ], may not always be accurate, as the provision of nutritional support becomes more sophisticated and specific. For instance, it is now possible to integrate nutritional supplements with anabolic or anti-catabolic agents [
      • Gullett N.P.
      • Mazurak V.C.
      • Hebbar G.
      • et al.
      Nutritional interventions for cancer-induced cachexia.
      ], to better treat the cachectic status compared to using standard nutritional support.
      Cachexia is commonly associated with inadequate nutrient intake leading to a general state of deterioration and deconditioning, decreased or absent physical activity, and altered metabolism due to a pathological systemic inflammatory response [
      • Aapro M.
      • Arends J.
      • Bozzetti F.
      • et al.
      Early recognition of malnutrition and cachexia in the cancer patient: a position paper of a European School of Oncology Task Force.
      ]. This condition can occur even in the absence of apparent weight loss, or prior to losing fat mass, and can be exacerbated by cancer therapy [
      • Fearon K.
      • Arends J.
      • Baracos V.
      Understanding the mechanisms and treatment options in cancer cachexia.
      ]. It may also be obscured by obesity, resulting in under-diagnosis and excess mortality [
      • Fearon K.
      • Arends J.
      • Baracos V.
      Understanding the mechanisms and treatment options in cancer cachexia.
      ]. The cancer itself and its related treatments often cause taste and smell alterations, appetite loss, swallowing and absorption disorders, and enhanced catabolism [
      • Fearon K.
      • Strasser F.
      • Anker S.D.
      • et al.
      Definition and classification of cancer cachexia: an international consensus.
      ], leading to higher nutritional risk. In the absence of appropriate intervention, loss of substantial muscle mass is almost inevitable and will eventually lead to progressive cachexia. Management is therefore multidimensional, and involves early initiation of nutritional care or support, resistance exercises to prevent muscle atrophy, endurance exercises to counteract fatigue, and treatment of inflammation-related hypermetabolic state [
      • Fearon K.
      • Strasser F.
      • Anker S.D.
      • et al.
      Definition and classification of cancer cachexia: an international consensus.
      ] where possible.

      1.3 Gastrointestinal Cancers

      Nutritional risk, although common in older adults with cancer, is notably higher in patients with GI malignancies, particularly in the presence of GI symptoms [
      • Palesty J.A.
      • Dudrick S.J.
      What we have learned about cachexia in gastrointestinal cancer.
      ] such as, anorexia, early satiety, nausea, vomiting, dysphagia, odynophagia, diarrhea, constipation, malabsorption, and pain. In some patients, unintentional weight loss, mostly from GI symptoms, is present long before the diagnosis of malignancy is made. Weight loss at presentation has been associated with reduced ability to tolerate anti-cancer therapy, increased severe dose-limiting toxicities, lesser response rates, worse QoL, decline in performance status, and shorter survival outcomes among patients with locally advanced or metastatic GI cancers [
      • Andreyev H.J.N.
      • Norman A.R.
      • Oates J.
      • et al.
      Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies?.
      ]. The prevalence varies depending on the definition used in the literature and the GI cancer type – 28–54% in hepatocellular, 39–71% in colorectal, and 56% in pancreatic cancers [
      • Ryan A.M.
      • Power D.G.
      • Daly L.
      • et al.
      Cancer-associated malnutrition, cachexia and sarcopenia: the skeleton in the hospital closet 40 years later.
      ].
      Several prospective and retrospective studies have linked nutritional impairments in GI cancers with negative outcomes as shown in Table 2. Nutritional status screening of 1453 patients with cancer (median age 64, range 55–71, 64% had GI cancers), in the outpatient setting using the Nutritional Risk Score (NRS-2002) of ≥3 as “at-risk”, reported a 22% high nutritional-risk rate among patients with GI cancer, particularly in the presence of worsening performance status, fatigue and anorexia symptoms [
      • Bozzetti F.
      • Mariani L.
      • Lo Vullo S.
      • et al.
      The nutritional risk in oncology: a study of 1,453 cancer outpatients.
      ]. In a cross-sectional study of 313 patients (mean age 63 years) with GI cancers, the malnutrition rate was 52%, where 25% was severe and underestimated by the treating physicians [
      • Attar A.
      • Malka D.
      • Sabate J.M.
      • et al.
      Malnutrition is high and underestimated during chemotherapy in gastrointestinal cancer: an AGEO prospective cross-sectional multicenter study.
      ]. Among patients aged ≥70 years (30%), 39% had moderate and 18% had severe malnutrition [
      • Attar A.
      • Malka D.
      • Sabate J.M.
      • et al.
      Malnutrition is high and underestimated during chemotherapy in gastrointestinal cancer: an AGEO prospective cross-sectional multicenter study.
      ]. Factors associated with severe malnutrition include performance status, ≥3 prior lines of treatment, pancreatic, and gastric cancers [
      • Attar A.
      • Malka D.
      • Sabate J.M.
      • et al.
      Malnutrition is high and underestimated during chemotherapy in gastrointestinal cancer: an AGEO prospective cross-sectional multicenter study.
      ]. Malnutrition has also led to increased incidence of perioperative complications (i.e. infections, delayed wound healing, wound dehiscence, etc.), poorer tolerance or augmented toxicities to treatment, altered QoL, higher hospital costs, and mortality [
      • French Speaking Society of Clinical N and Metabolism
      Clinical nutrition guidelines of the French Speaking Society of Clinical Nutrition and Metabolism (SFNEP): summary of recommendations for adults undergoing non-surgical anticancer treatment.
      ]. In a cohort study associating sarcopenia with postoperative morbidity and mortality after CRC surgery (n = 310), 51.3% of patients were aged >70 years; age was an independent predictor of mortality, and sarcopenia was associated with a higher 30-day or in-hospital mortality (8.8% vs. 0.7%) [
      • Reisinger K.W.
      • van Vugt J.L.
      • Tegels J.J.
      • et al.
      Functional compromise reflected by sarcopenia, frailty, and nutritional depletion predicts adverse postoperative outcome after colorectal cancer surgery.
      ]. A combination of instruments assessing function, nutrition, frailty, and sarcopenia can accurately predict post-operative sepsis [
      • Reisinger K.W.
      • van Vugt J.L.
      • Tegels J.J.
      • et al.
      Functional compromise reflected by sarcopenia, frailty, and nutritional depletion predicts adverse postoperative outcome after colorectal cancer surgery.
      ]. In a multicentre study including 51 metastatic CRC patients (median age 65 years), sarcopenia was associated with grade 3–4 chemotherapy toxicities (odds ratio, OR 13.55, p = 0.043) [
      • Barret M.
      • Antoun S.
      • Dalban C.
      • et al.
      Sarcopenia is linked to treatment toxicity in patients with metastatic colorectal cancer.
      ]. Similarly, sarcopenia was a significant predictor of dose limiting toxicity in patients with esophago-gastric cancer (n = 89, median age 65.8 years) receiving neoadjuvant chemotherapy (OR 2.95; 95% confidence interval, CI 1.23–7.09; p = 0.015) [
      • Tan B.H.
      • Brammer K.
      • Randhawa N.
      • et al.
      Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer.
      ], while NRS-2002 ≥3 was an independent adverse prognostic factor in 830 patients with gastric cancer (48% aged ≥70 years), where the median survival for NRS-2002 <3 was 31.9 months vs. 25.7 months for NRS-2002 ≥3 (p < 0.001) [
      • Qiu M.
      • Zhou Y.X.
      • Jin Y.
      • et al.
      Nutrition support can bring survival benefit to high nutrition risk gastric cancer patients who received chemotherapy.
      ].
      Older patients on chemotherapy who are “at risk” of malnutrition according to the MNA have a 2-fold increase in 1-year mortality [
      • Aaldriks A.A.
      • Maartense E.
      • le Cessie S.
      • et al.
      Predictive value of geriatric assessment for patients older than 70 years, treated with chemotherapy.
      ]. Likewise, a higher 1-year mortality (OR 2.77) was noted in malnourished older (≥70 years) patients treated with first-line chemotherapy [
      • Soubeyran P.
      • Fonck M.
      • Blanc-Bisson C.
      • et al.
      Predictors of early death risk in older patients treated with first-line chemotherapy for cancer.
      ]. In a prospective study of 143 patients aged ≥70 years with CRC, poor MNA score not only increased the risk of mortality in patients receiving palliative chemotherapy (HR 2.76, 95% CI 1.60–4.77; p < 0.001) but also predicted for less tolerance to chemotherapy (p = 0.008) [
      • Aaldriks A.A.
      • van der Geest L.G.
      • Giltay E.J.
      • et al.
      Frailty and malnutrition predictive of mortality risk in older patients with advanced colorectal cancer receiving chemotherapy.
      ]. Cachexia was associated with poorer survival and performance status in pancreatic cancer, independent of tumor size and metastatic load [
      • Bachmann J.
      • Heiligensetzer M.
      • Krakowski-Roosen H.
      • et al.
      Cachexia worsens prognosis in patients with resectable pancreatic cancer.
      ]. Interestingly, sarcopenia alone was not predictive of decreased survival in a systematic review of pancreatic cancer [
      • Ozola Zalite I.
      • Zykus R.
      • Francisco Gonzalez M.
      • et al.
      Influence of cachexia and sarcopenia on survival in pancreatic ductal adenocarcinoma: a systematic review.
      ]. A recent systematic review and meta-analysis (37 studies, 56% with GI cancers) of the prognostic value of low skeletal muscle index obtained from CT screening on any solid tumors at various stages demonstrated that sarcopenia was associated with worse cancer-specific and disease-free survival [
      • Shachar S.S.
      • Williams G.R.
      • Muss H.B.
      • et al.
      Prognostic value of sarcopenia in adults with solid tumours: a meta-analysis and systematic review.
      ].

      2. Management Approach From a Geriatric Oncologist's Perspective

      Weight loss of as little as 5% of body weight has been linked to lower survival and treatment response in patients with cancer [
      • Dewys W.D.
      • Begg C.
      • Lavin P.T.
      • et al.
      Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.
      ]. For patients with colon, gastric, and pancreatic cancers, survival improvement without weight loss was 51%, 33%, and 14%, respectively relative to survival with weight loss [
      • Dewys W.D.
      • Begg C.
      • Lavin P.T.
      • et al.
      Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.
      ]. In addition, poor performance status has been directly correlated with weight loss, suggesting that muscle loss may impact the level of activity [
      • Dewys W.D.
      • Begg C.
      • Lavin P.T.
      • et al.
      Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group.
      ]. Therefore, it is recommended to evaluate the nutritional status of all patients undergoing oncological treatment [
      • French Speaking Society of Clinical N and Metabolism
      Clinical nutrition guidelines of the French Speaking Society of Clinical Nutrition and Metabolism (SFNEP): summary of recommendations for adults undergoing non-surgical anticancer treatment.
      ] from the time of cancer diagnosis and repeated as clinically indicated for inadequate nutritional intake, weight loss, and low BMI, and to assess for treatable nutrition impact symptoms and metabolic derangements if found to be “at risk” [
      • Arends J.
      • Bachmann P.
      • Baracos V.
      • et al.
      ESPEN guidelines on nutrition in cancer patients.
      ]. Evaluation could be as simple as serial measurement of body weight, or by using nutritional screening tools, which are quick and easily completed by any health staff, or with a more exhaustive nutritional assessment, performed by trained personnel. Such evaluation may be particularly more relevant to perform in older patients with cancer, as nutritional impairments are more prevalent, yet easily overlooked without proper assessment [
      • Evans C.
      Malnutrition in the elderly: a multifactorial failure to thrive.
      ,
      • Hickson M.
      Malnutrition and ageing.
      ]. As the process of aging occurs at a heterogeneous pace, the International Society of Geriatric Oncology (SIOG) recommends that all older patients with cancer, especially those considered for anticancer treatment, undergo a comprehensive geriatric assessment (CGA) [
      • Wildiers H.
      • Heeren P.
      • Puts M.
      • et al.
      International Society of Geriatric Oncology consensus on geriatric assessment in older patients with cancer.
      ], which includes the evaluation of comorbidity, function, nutrition, psychosocial status, and presence of geriatric syndromes, as these provide multidimensional information on the patients' over-all health status that may be predictive of mortality and treatment tolerance.

      2.1 Nutritional Assessment Tools in Older Adults With GI Cancers

      Much information can be gleaned from a full nutritional assessment, but as with any comprehensive assessment tool, it is time-consuming and requires specialized nutritional expertise, hence it may be impractical to use in all patients in a busy oncology clinic. Screening tools are more useful in this setting and only malnourished patients and those at risk of malnutrition on screening are referred for a full nutritional assessment and intervention. Validated nutritional screening tools, such as the Malnutrition Screening Tool (MST) [
      • Ferguson M.
      • Capra S.
      • Bauer J.
      • et al.
      Development of a valid and reliable malnutrition screening tool for adult acute hospital patients.
      ], the Mini-Nutritional Assessment Short Form Revised (MNA-SF) [
      • Kaiser M.J.
      • Bauer J.M.
      • Ramsch C.
      • et al.
      Validation of the Mini Nutritional Assessment short-form (MNA-SF): a practical tool for identification of nutritional status.
      ], the Nutrition Risk Screening (NRS-2002) [
      • Kondrup J.
      Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials.
      ], and the Malnutrition Universal Screening Tool (MUST) [
      • BAPEN
      Malnutrition Universal Screening Tool (MUST). The British Association for Parenteral and Enteral Nutrition.
      ] may be used in older oncology patients, though these screening tools have not been evaluated specifically for older adults with GI malignancies. Table 3 summarises the variables assessed, cut-off values and proposed interventions in these screening tools. There remains no gold standard for nutritional screening and which cut-off values to use to initiate further assessment, as none of these tools were designed specifically for diagnostic, prognostic, or interventional purposes. Despite the lack of expert consensus on which tool to use, particularly in older patients with cancer, it is clear that screening with any of the validated tools mentioned, at the very least, should be performed at the time of diagnosis, on admission to hospitals or care homes, during clinic follow-ups, and at regular intervals depending on clinical status [
      • Isenring E.
      • Elia M.
      Which screening method is appropriate for older cancer patients at risk for malnutrition?.
      ]. Selection of the most appropriate screening tool is based on setting, familiarity, and practicality [
      • Bauer J.M.
      • Kaiser M.J.
      • Sieber C.C.
      Evaluation of nutritional status in older persons: nutritional screening and assessment.
      ].
      Table 3Nutritional screening tools.
      ToolVariablesAbnormal scoreIntervention
      Malnutrition Screening Tool
      • Ferguson M.
      • Capra S.
      • Bauer J.
      • et al.
      Development of a valid and reliable malnutrition screening tool for adult acute hospital patients.
      1. Have you or the patient lost weight recently without trying?2Dietician referral for full assessment and intervention

      Monitor weight

      Rescreen patients
       No0
       Unsure2
       Yes, how much (kg)
      1–51
      6–102
      10–143
      154
      Unsure2
      2. Have you or the patient been eating poorly because of decreased appetite?
       No0
       Yes1
      Mini-Nutritional Assessment-Short Form Revised
      • Kaiser M.J.
      • Bauer J.M.
      • Ramsch C.
      • et al.
      Validation of the Mini Nutritional Assessment short-form (MNA-SF): a practical tool for identification of nutritional status.
      A. Has food intake declined over the past 3 months due to loss of appetite, digestive problems, chewing or swallowing difficulties?12–14

      8–11

      0–7
      Normal

      At risk

      Malnourished
       Severe decrease0
       Moderate decrease1
       No decrease2
      B. Weight loss during the last 3 months
       >3 kg (6.6 lb)0
       Does not know1
       1–3 kg (2.2–6.6 lb)2
       None3
      C. Mobility
       Bed or chair bound0
       Out of bed or chair1
       Goes out2
      D. Has suffered psychological stress or acute disease in the past 3 months?
       Yes0
       No2
      E. Neuropsychological problems
       Severe dementia or depression0
       Mild dementia1
       None2
      F.
       1. Body mass index (BMI), weight in kg/height in m2
      Less than 190
      19–less than 211
      21–less than 232
      23 or greater3
       2. Calf circumference (CC) in cm
      <310
      313
      Nutritional Risk Screening (NRS 2002)
      • Kondrup J.
      Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials.
      Part 1. Initial screening
       Yes or noBMI < 20.5

      Weight loss in 3 months

      Reduced dietary intake in the last week

      Severely ill
      If the answer is yes to any questionsProceed to Part 2
      If the answer is no to all the questionsRe-screen patient at weekly intervals

      If the patient is at risk, e.g. scheduled for a major operation, consider a preventative nutritional care plan
      Part 2. Final screening
       Impaired nutritional statusAdd total score:
      0 AbsentNormal3At risk: initiate nutritional care plan
      1 MildWeight loss (WL) >5% in 3 months or food intake (FI) <50–75% of normal requirement in preceding week
      2 ModerateWL >5% in 2 months or BMI 18.5–20.5 + impaired general condition or FI 25–60% of normal requirement in preceding week
      3 SevereWL >5% in 1 month (>15% in 3 months) or BMI <18.5 + impaired general condition or FI 0–25% of normal requirement in preceding week
       Severity of disease
      0 AbsentNormal<3Re-screen patient at weekly intervals

      If the patient is at risk, e.g. scheduled for a major operation, consider a preventative nutritional care plan
      1 MildHip fracture; acute complications of chronic disease; cirrhosis; COPD; diabetes; hemodialysis; oncology
      2 ModerateMajor abdominal surgery; stroke; severe pneumonia; hematologic malignancy
      3 SevereHead injury; bone marrow transplant; ICU (APACHE > 10)
      Age if ≥70 years: add 1 to total score
      Malnutrition Universal Screening Tool (MUST)
      • BAPEN
      Malnutrition Universal Screening Tool (MUST). The British Association for Parenteral and Enteral Nutrition.
      5 steps to measure:4. Add scores to calculate overall risk of malnutrition5. Management
       1. BMIOverall scoreRisk of malnutrition
      (BMI kg/m2)Score0LowRoutine clinical care

      Repeat screening

      In-patient: weekly

      Care homes: monthly

      Community: annually
      >20 (>30 obese)0
      18.5–201
      <18.52
       2. Unplanned weight loss in past 3–6 months
      (%)Score1MediumObserve

      Document dietary intake for 3 days

      If adequate: no concerns, repeat screening:

      In-patient: weekly

      Care homes: monthly

      Community: every 2–3 months

      If inadequate: clinical concern – follow local policy, set goals, improve and increase overall nutritional intake, monitor and review care plan regularly
      <50
      5–101
      >102
       3. Effect of acute disease
      Acutely ill, presence or probability of no nutritional intake for >5 daysScore2HighTreat*

      Refer to dietician, nutritional support team, or implement local policy

      Set goals, improve and increase nutritional intake

      Monitor and review care plan:

      In-patient: weekly

      Care homes: monthly

      Community: monthly
      2
      *Unless no benefit is expected from nutritional support, e.g. imminent death

      All risk categories:
      • Treat underlying condition and provide help and advice on food choices, eating, drinking when necessary
      • Record malnutrition risk category
      • Record need for special diets and follow local policy
      Re-assess subjects identified at risk as they move through care settings
      A more specific assessment, such as the MNA, should follow an abnormal screening test to detect which patients might benefit from appropriately designed interventions [
      • Arends J.
      • Bachmann P.
      • Baracos V.
      • et al.
      ESPEN guidelines on nutrition in cancer patients.
      ]. The MNA is a well-established and validated nutritional assessment tool in older adults, consisting of 18 items grouped in 4 headings: anthropometric measurements (BMI, weight loss, arm and calf circumferences), general assessment (lifestyle, medication, mobility, and presence of depression or dementia), short dietary assessment (number of meals, food, and fluid intake, and feeding autonomy), and subjective assessment (self-perception of health and nutrition) [
      • Guigoz Y.
      The mini Nutritional Assessment (MNA®) review of the literature - what does it tell us?.
      ]. The maximum score is 30, with threshold values of ≥24 for well-nourished, 17–23.5 for at-risk, and <17 for malnourished. The sensitivity, specificity, and positive predictive values according to the clinical status were 96%, 98%, and 97%, respectively [
      • Guigoz Y.V.B.
      • Garry P.J.
      Mini Nutritional Assessment (MNA): research and practice in the elderly.
      ]. It has been correlated with cancer cachexia features [
      • Gioulbasanis I.
      • Georgoulias P.
      • Vlachostergios P.J.
      • et al.
      Mini Nutritional Assessment (MNA) and biochemical markers of cachexia in metastatic lung cancer patients: interrelations and associations with prognosis.
      ] and was one of the independent predictors for chemotherapy toxicity [
      • Extermann M.
      • Boler I.
      • Reich R.R.
      • et al.
      Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score.
      ] and early death [
      • Soubeyran P.
      • Fonck M.
      • Blanc-Bisson C.
      • et al.
      Predictors of early death risk in older patients treated with first-line chemotherapy for cancer.
      ,
      • AME Aaldriks
      • Giltay E.J.
      • et al.
      The impact of geriatric assessment on the outcome of older breast cancer patients treated with chemotherapy (abstract).
      ,
      • Bourdel-Marchasson I.
      • Diallo A.
      • Bellera C.
      • et al.
      One-year mortality in older patients with cancer: development and external validation of an MNA-based prognostic score.
      ].
      More recently, other assessment tools have been studied using scoring systems. Martin et al. developed a cancer weight loss grading system incorporating %weight loss and BMI that predicted nearly a 5-fold difference in median survival between grades 0 (least risk) and 4 (highest risk), independent of cancer site, stage, and performance status [
      • Martin L.
      • Senesse P.
      • Gioulbasanis I.
      • et al.
      Diagnostic criteria for the classification of cancer-associated weight loss.
      ]. The Patient- and Nutrition-Derived Outcome Risk Assessment Score (PANDORA) is a simple risk scoring system that includes age, BMI, mobility, nutrient intake, main patient group, cancer, and fluid status, and has been validated to predict 30-day hospital mortality [
      • Hiesmayr M.
      • Frantal S.
      • Schindler K.
      • et al.
      The Patient- And Nutrition-Derived Outcome Risk Assessment Score (PANDORA): development of a simple predictive risk score for 30-day in-hospital mortality based on demographics, clinical observation, and nutrition.
      ]. Specific to older patients, a nomogram was developed based on CGA factors in older patients with cancer, showing that advanced stage, anemia, depression, and poor ECOG performance status were independently predictive of moderate to high-risk of malnutrition [
      • Tan T.
      • Ong W.S.
      • Rajasekaran T.
      • et al.
      Identification of comprehensive geriatric assessment based risk factors for malnutrition in elderly Asian cancer patients.
      ]. However, use of the scoring system is yet to be validated in clinical practice. The lack of a gold standard for both screening and full nutritional assessment tools highlights the dearth of research focusing on validated tools to measure malnutrition.

      2.2 Role of Nutritional, Pharmacologic & Physical Intervention in Older Adults With GI Cancers

      An oncologist is expected to know about patient-, disease-, and treatment-related factors, and therefore has the critical responsibility of identifying patients who will potentially benefit from nutritional support and strategies, including knowing when to refer to dieticians and integrate the nutritional plan within the oncologic regimen [
      • Bozzetti F.
      The oncologist as coordinator of the nutritional approach.
      ]. Although it is clear that a specific intervention is needed to counteract and manage the deleterious effects of malnutrition, the efficacy and choice of interventional strategies remain contentious, and evidence for nutritional management specific to older patients with GI cancers is lacking. In addition to aging heterogeneity, the patient's nutritional needs vary according to disease site, cancer stage, disease burden, and comorbidities that may limit treatment generalization. Algorithms for managing nutritional needs of older patients with cancer with GI cancers are illustrated in Fig. 1, Fig. 2, which may be used as a guide for the treating oncologist.
      Fig. 1
      Fig. 1Nutritional management algorithm for older patients with gastrointestinal cancers.
      Fig. 2
      Fig. 2Strategies for nutritional approach in a malnourished GI cancer patient.

      2.2.1 Nutritional Intervention

      Nutritional counselling, which includes dietary history, diagnosis, and therapy, is recommended to malnourished patients with GI cancers requiring chemotherapy [
      • Senesse P.
      • Assenat E.
      • Schneider S.
      • et al.
      Nutritional support during oncologic treatment of patients with gastrointestinal cancer: who could benefit?.
      ], and is usually performed by trained dieticians [
      • Arends J.
      • Bachmann P.
      • Baracos V.
      • et al.
      ESPEN guidelines on nutrition in cancer patients.
      ]. Individualized dietary counselling of patients receiving chemotherapy and/or radiotherapy for esophageal or gastric cancers has been associated with improved weight maintenance, energy- and protein-intake without any significant effects on QoL, treatment-related toxicities, or prevalence of micronutrient deficiencies [
      • Poulsen G.M.
      • Pedersen L.L.
      • Osterlind K.
      • et al.
      Randomized trial of the effects of individual nutritional counseling in cancer patients.
      ]. In contrast, a proportional improvement of QoL with adequate nutritional status was observed among patients with CRC receiving radiotherapy [
      • Ravasco P.
      • Monteiro-Grillo I.
      • Vidal P.M.
      • et al.
      Dietary counseling improves patient outcomes: a prospective, randomized, controlled trial in colorectal cancer patients undergoing radiotherapy.
      ]. Notably, dietary counselling is an individualized, time-consuming process, which often fails when used in already severely anorectic patients, although it appears effective in patients with digestive problems caused by radiation or chemotherapy [
      • Isenring E.
      • Zabel R.
      • Bannister M.
      • et al.
      Updated evidence-based practice guidelines for the nutritional management of patients receiving radiation therapy and/or chemotherapy.
      ]. The effect of dietary interventions on QoL, based on two systematic reviews and meta-analyses [
      • Halfdanarson T.R.
      • Thordardottir E.
      • West C.P.
      • Jatoi A.
      Does dietary counseling improve quality of life in cancer patients? A systematic review and meta-analysis.
      ,
      • Baldwin C.
      • Spiro A.
      • Ahern R.
      • et al.
      Oral nutritional interventions in malnourished patients with cancer: a systematic review and meta-analysis.
      ], remains inconclusive, particularly among patients receiving chemotherapy. Moreover, no trials have shown any benefit on mortality [
      • Baldwin C.
      • Spiro A.
      • Ahern R.
      • et al.
      Oral nutritional interventions in malnourished patients with cancer: a systematic review and meta-analysis.
      ,
      • Baldwin C.
      • Spiro A.
      • McGough C.
      • et al.
      Simple nutritional intervention in patients with advanced cancers of the gastrointestinal tract, non-small cell lung cancers or mesothelioma and weight loss receiving chemotherapy: a randomised controlled trial.
      ,
      • Evans W.K.
      • Nixon D.W.
      • Daly J.M.
      • et al.
      A randomized study of oral nutritional support versus ad lib nutritional intake during chemotherapy for advanced colorectal and non-small-cell lung cancer.
      ] and similar results were found in older populations with cancers [
      • Bourdel-Marchasson I.
      • Blanc-Bisson C.
      • Doussau A.
      • et al.
      Nutritional advice in older patients at risk of malnutrition during treatment for chemotherapy: a two-year randomized controlled trial.
      ]. As some nutritional interventions may not always be feasible, particularly in institutions not equipped with specific “nutritional units” to accommodate a large number of patients needing intervention, it is critical to personalize and tailor interventions to each institution's available resources (Fig. 1).
      Although the best way to maintain or increase energy- and protein-intake is with normal food, it is often difficult and nutritional supplements are often required. Specific to GI cancers, where problems with dysgeusia, early satiety, nausea, vomiting, or compromised gastric or intestinal transit are more prevalent, the utility of an oral approach may be limited. If oral intake is deemed inadequate or impossible, either due to the disease or treatment, then supportive feeding, via enteral or parenteral feeding, may be considered (Fig. 2), taking into account the goal of treatment (curative vs. palliative), disease trajectory, estimated life expectancy, and with anticipated benefits weighed against the potential risks, burdens, and costs. Enteral feeding (oral supplements ± intensive counselling or tube feeding) may be as efficient as parenteral feeding, particularly if intestinal functions are preserved [
      • Bozzetti F.
      Nutritional support in patients with oesophageal cancer.
      ], and provides the added benefit of maintaining the gut barrier, fewer infectious complications, and lower costs [
      • Arends J.
      • Bachmann P.
      • Baracos V.
      • et al.
      ESPEN guidelines on nutrition in cancer patients.
      ]. The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines on enteral nutrition in the older population recommend the use of gastrostomy for long-term (≥4 weeks) nutritional support over nasogastric tubes due to fewer treatment failures, better nutritional status, and convenience to the patient [
      • Volkert D.
      • Berner Y.N.
      • Berry E.
      • et al.
      ESPEN Guidelines on Enteral Nutrition: geriatrics.
      ]. However, there is no significant difference in the clinical benefit between nasogastric and gastrostomy feeding [
      • Bozzetti F.
      Tube feeding in the elderly cancer patient.
      ] in terms of infection rate and survival outcomes in a systematic review of studies conducted in patients with head and neck cancers [
      • Wang J.
      • Liu M.
      • Liu C.
      • et al.
      Percutaneous endoscopic gastrostomy versus nasogastric tube feeding for patients with head and neck cancer: a systematic review.
      ]. The ESPEN recommends that nutritional therapy should be started if malnutrition already exists or if it is anticipated that the patient will not be able to eat for >7 days [
      • Arends J.
      • Bachmann P.
      • Baracos V.
      • et al.
      ESPEN guidelines on nutrition in cancer patients.
      ].
      If enteral nutrition is not feasible, contraindicated, or not tolerable in malnourished cancer patients, then short-term parenteral nutrition may be considered, particularly in patients with acute GI complications from surgery, chemotherapy and/or radiotherapy (e.g. severe radiation enteritis or severe malabsorption) [
      • Bozzetti F.
      • Arends J.
      • Lundholm K.
      • et al.
      ESPEN Guidelines on Parenteral Nutrition: non-surgical oncology.
      ]. This decision must be balanced against a realistic outlook for recovery [
      • Sobotka L.
      • Schneider S.M.
      • Berner Y.N.
      • et al.
      ESPEN Guidelines on Parenteral Nutrition: geriatrics.
      ] and prognosis. Of note, the risk of developing refeeding syndrome increases with the degree of nutritional depletion and must be monitored and managed pre-emptively [
      • Walmsley R.S.
      Refeeding syndrome: screening, incidence, and treatment during parenteral nutrition.
      ].
      Patients with rapidly progressive disease with poor performance status and limited life expectancy are less likely to benefit from aggressive nutritional interventions. However, trial of oral or less invasive nutritional support may be offered to provide symptomatic or comfort care [
      • Arends J.
      • Bachmann P.
      • Baracos V.
      • et al.
      ESPEN guidelines on nutrition in cancer patients.
      ]. Long-term (home) parenteral nutrition (HPN) may be considered in patients with subacute or chronic radiation enteropathy, or as a palliative nutritional support in hypophagic or (sub)obstructed patients with acceptable performance status, or in patients who are expected to die sooner from starvation rather than cancer [
      • Bozzetti F.
      • Arends J.
      • Lundholm K.
      • et al.
      ESPEN Guidelines on Parenteral Nutrition: non-surgical oncology.
      ]. Among 414 cachectic (sub)obstructed, incurable patients (41% were ≥65 years and 56% had GI cancers), HPN has been associated with a longer 3- and 6-month survival (than is expected with total macronutrient deprivation) and varies considerably with Karnofsky performance status and Glasgow prognostic score [
      • Bozzetti F.
      • Santarpia L.
      • Pironi L.
      • et al.
      The prognosis of incurable cachectic cancer patients on home parenteral nutrition: a multi-centre observational study with prospective follow-up of 414 patients.
      ]. Complications from long-term enteral (tube obstruction or displacement, diarrhea, or constipation) or parenteral (infections, thrombosis, or obstruction) nutrition are similar regardless of age [
      • Schneider S.M.
      • Hebuterne X.
      Nutritional support of the elderly cancer patient: long-term nutritional support.
      ], although a higher risk for central catheter vascular erosion (p = 0.009) [
      • Walshe C.
      • Phelan D.
      • Bourke J.
      • et al.
      Vascular erosion by central venous catheters used for total parenteral nutrition.
      ] was seen in older compared to younger patients.

      2.2.2 Pharmacologic Intervention

      Supportive drugs, such as antiemetics to relieve nausea, analgesics to relieve pain associated with swallowing or other GI activity, motility agents to treat constipation or diarrhea, prokinetics to improve intestinal transit, and pharmaconutrients such as ω3 fatty acids to improve appetite and body weight, may be used to target the main pathogenic mechanisms of cancer cachexia [
      • Arends J.
      • Bachmann P.
      • Baracos V.
      • et al.
      ESPEN guidelines on nutrition in cancer patients.
      ]. Corticosteroids may increase appetite, control pain, alleviate nausea or vomiting, and improve QoL [
      • Yavuzsen T.
      • Davis M.P.
      • Walsh D.
      • et al.
      Systematic review of the treatment of cancer-associated anorexia and weight loss.
      ] but may only be used for a restricted period of time (1–3 weeks), due to early loss of efficacy [
      • Moertel C.G.
      • Schutt A.J.
      • Reitemeier R.J.
      • et al.
      Corticosteroid therapy of preterminal gastrointestinal cancer.
      ], and the side-effects with long-term use may be more problematic in the elderly where sarcopenia, insulin resistance, infections, or delirium are more prevalent. Thus, corticosteroids may be more useful in the palliative setting among patients with limited life expectancy [
      • Miller S.
      • Mc Nutt L.
      • McCann M.A.
      • et al.
      Use of corticosteroids for anorexia in palliative medicine: a systematic review.
      ]. There is insufficient evidence to recommend any particular corticosteroid drug over another, or recommend a dosing regimen [
      • Miller S.
      • Mc Nutt L.
      • McCann M.A.
      • et al.
      Use of corticosteroids for anorexia in palliative medicine: a systematic review.
      ]. Progestins (megestrol acetate and medroxyprogesterone acetate) increase appetite, caloric intake and body weight but not fat-free mass, with minimal effect on QoL [
      • Yavuzsen T.
      • Davis M.P.
      • Walsh D.
      • et al.
      Systematic review of the treatment of cancer-associated anorexia and weight loss.
      ] and higher rates of edema, thromboembolism, and deaths [
      • Yavuzsen T.
      • Davis M.P.
      • Walsh D.
      • et al.
      Systematic review of the treatment of cancer-associated anorexia and weight loss.
      ]. ω3 fatty acids (fish oil) improve appetite, oral intake, lean body mass and body weight in patients with advanced cancer and at risk of malnutrition [
      • Arends J.
      • Baracos V.
      • Bertz H.
      • et al.
      ESPEN expert group recommendations for action against cancer-related malnutrition.
      ]. A non-significant delay in time to tumor progression was noted when supplemental 2 g/day of fish oil was given to patients with advanced CRC in the first 9 weeks of chemotherapy [
      • Camargo Cde Q.
      • Mocellin M.C.
      • Pastore Silva Jde A.
      • et al.
      Fish oil supplementation during chemotherapy increases posterior time to tumor progression in colorectal cancer.
      ]. Less chemotherapy-induced stomatitis and diarrhea, and more hepatoprotective effects were noted with ω3-rich enteral nutrition support than with the ω3-poor formulation, among 61 patients (mean age 64.5 ± 8.4 years) who received neoadjuvant chemotherapy for esophageal cancer. Branched-chain amino acids, especially leucine, promote muscle protein synthesis in older adults, provided that renal function is not severely impaired [
      • Deutz N.E.
      • Bauer J.M.
      • Barazzoni R.
      • et al.
      Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group.
      ]. There are insufficient consistent clinical data to recommend use of cannabinoids to improve appetite [
      • Cannabis In Cachexia Study G
      • Strasser F.
      • Luftner D.
      • et al.
      Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group.
      ,
      • Jatoi A.
      • Windschitl H.E.
      • Loprinzi C.L.
      • et al.
      Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study.
      ] or the use of NSAIDs to increase body weight [
      • Solheim T.S.
      • Fearon K.C.
      • Blum D.
      • et al.
      Non-steroidal anti-inflammatory treatment in cancer cachexia: a systematic literature review.
      ], amino acids to improve fat-free mass [
      • Berk L.
      • James J.
      • Schwartz A.
      • et al.
      A randomized, double-blind, placebo-controlled trial of a beta-hydroxyl beta-methyl butyrate, glutamine, and arginine mixture for the treatment of cancer cachexia (RTOG 0122).
      ], or androgenic steroids to boost muscle mass [
      • Loprinzi C.L.
      • Kugler J.W.
      • Sloan J.A.
      • et al.
      Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia.
      ].

      2.2.3 Physical Intervention

      There is a strong association between physical activities and preservation of body composition among highly active older adults [
      • Kohrt W.M.
      • Obert K.A.
      • Holloszy J.O.
      Exercise training improves fat distribution patterns in 60- to 70-year-old men and women.
      ]. Physical activities in patients with cancer have been associated with improved aerobic fitness, muscle strength, health-related QoL, and psychological benefits [
      • Speck R.M.
      • Courneya K.S.
      • Masse L.C.
      • et al.
      An update of controlled physical activity trials in cancer survivors: a systematic review and meta-analysis.
      ,
      • Fong D.Y.
      • Ho J.W.
      • Hui B.P.
      • et al.
      Physical activity for cancer survivors: meta-analysis of randomised controlled trials.
      ]. However, most of these studies were conducted in women with early stage breast cancers who clearly have different demands compared to patients with GI cancers. Combinations of resistance exercises and aerobic muscle training may provide significant benefit in physical performance [
      • Argiles J.M.
      • Busquets S.
      • Lopez-Soriano F.J.
      • et al.
      Are there any benefits of exercise training in cancer cachexia?.
      ], at least among patients who are not limited by extreme fatigue. The ESPEN recommends all older people to undertake daily physical activities (resistance training, aerobic exercise) for as long as possible [
      • Deutz N.E.
      • Bauer J.M.
      • Barazzoni R.
      • et al.
      Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group.
      ]. However, data specific to older patients with GI cancer are lacking. Physical activity may ameliorate the age-related decrease in energy expenditure, and individualized physical interventions to reduce inactivity and avoidance of a sedentary lifestyle are essential [
      • Arends J.
      • Bachmann P.
      • Baracos V.
      • et al.
      ESPEN guidelines on nutrition in cancer patients.
      ].

      3. Palliative and Ethical Considerations

      As with any older patients with malignancy, nutritional treatment goals must be individualized within the context of the disease trajectory or prognosis, overall health status or life expectancy, and patient preferences. Timely palliative care and social work referrals may be necessary to provide a holistic psycho-emotional assessment and support to address the impact of sarcopenia or cancer cachexia. Discussion with patients (and caregivers) regarding artificial nutritional and hydration must be done as early as possible, particularly in the setting of a pre-terminal stage when such interventions are futile. Nevertheless, a short trial with a pre-specified endpoint may be considered in select cases of prognostic uncertainty, with the understanding that the intervention will be discontinued if the patient derives no benefit or deteriorates with the intervention [
      • Bozzetti F.
      • Chasen M.
      • Giddings G.
      Chapter 6: nutritional support for the advanced cancer patient during best supportive care.
      ]. The decision to initiate, continue or withhold, or withdraw nutritional interventions in imminently dying patients is often challenging, and a rather controversial topic riddled with social, cultural, economic, and emotional implications, and is beyond the scope of this paper.

      4. Conclusion

      Nutritional risks are common in GI malignancies and in older patients with cancer. Inadequate nutrient intake often leads to deterioration of general state and deconditioning. Malnutrition in older patients with cancer is associated with poorer health outcomes, worse prognosis, and less tolerance to treatment. Screening for nutritional risks is essential upon diagnosis followed by further assessment if found at risk or abnormal, with regular monitoring thereafter. Interventions, including physical activities, dietary counselling, supplemental nutrition, and enteral or parenteral feedings should be considered in order to improve function, nutritional status, and possibly QoL. Management relies on a multidisciplinary effort between the oncologists, other health care professionals, and caregivers. In the absence of a well-defined consensus for managing the nutritional needs of older patients with GI cancers, personalized treatment with the use of good clinical judgement is crucial.

      Author Contributions

      Concept and design: A.R. Mislang, S. Di Donato, G. Mottino, L. Biganzoli, F. Bozzetti
      Manuscript writing and approval: A.R. Mislang, S. Di Donato, J. Hubbard, L. Krisna, G. Mottino, L. Biganzoli, F. Bozzetti

      Disclosures and Conflict of Interest Statements

      AM: declares no conflict of interest.
      SD: declares no conflict of interest.
      JH: Research funding (Mayo Clinic) from Senhwa Biosciences, Boston Biochemical, Genentech, Boehringer Ingelheim, and Merck. Advisory Boards (honorarium to Mayo Clinic) for Genentech and Boehringer Ingelheim.
      LK: declares no conflict of interest.
      GM: declares no conflict of interest.
      FB: declares no conflict of interest.
      LB: declares no conflict of interest.

      Acknowledgement

      We acknowledge the SIOG internal reviewing committee (R. Kanesvaran and C. Ripamonti) for providing feedback on the manuscript.

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